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Article ; Online: From NSAIDs to Glucocorticoids and Beyond.

Sinniah, Ajantha / Yazid, Samia / Flower, Rod J

2021 Volume 10, Issue 12

Abstract: Our interest in inflammation and its treatment stems from ancient times. Hippocrates used willow bark to treat inflammation, and many centuries later, salicylic acid and its derivative aspirin's ability to inhibit cyclooxygenase enzymes was discovered. ... ...

Abstract	Our interest in inflammation and its treatment stems from ancient times. Hippocrates used willow bark to treat inflammation, and many centuries later, salicylic acid and its derivative aspirin's ability to inhibit cyclooxygenase enzymes was discovered. Glucocorticoids (GC) ushered in a new era of treatment for both chronic and acute inflammatory disease, but their potentially dangerous side effects led the pharmaceutical industry to seek other, safer, synthetic GC drugs. The discovery of the GC-inducible endogenous anti-inflammatory protein annexin A1 (AnxA1) and other endogenous proresolving mediators has opened a new era of anti-inflammatory therapy. This review aims to recapitulate the last four decades of research on NSAIDs, GCs, and AnxA1 and their anti-inflammatory effects.
MeSH term(s)	Animals ; Anti-Inflammatory Agents, Non-Steroidal/pharmacology ; Anti-Inflammatory Agents, Non-Steroidal/therapeutic use ; Glucocorticoids/pharmacology ; Glucocorticoids/therapeutic use ; Humans ; Inflammation/drug therapy ; Inflammation/pathology ; Models, Biological
Chemical Substances	Anti-Inflammatory Agents, Non-Steroidal ; Glucocorticoids
Language	English
Publishing date	2021-12-14
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2661518-6
ISSN	2073-4409 ; 2073-4409
ISSN (online)	2073-4409
ISSN	2073-4409
DOI	10.3390/cells10123524
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article: Therapeutic Potential of Certain Terpenoids as Anticancer Agents: A Scoping Review.

Kamran, Sareh / Sinniah, Ajantha / Abdulghani, Mahfoudh A M / Alshawsh, Mohammed Abdullah

Cancers

2022 Volume 14, Issue 5

Abstract: Cancer is a life-threatening disease and is considered to be among the leading causes of death worldwide. Chemoresistance, severe toxicity, relapse and metastasis are the major obstacles in cancer therapy. Therefore, introducing new therapeutic agents ... ...

Abstract	Cancer is a life-threatening disease and is considered to be among the leading causes of death worldwide. Chemoresistance, severe toxicity, relapse and metastasis are the major obstacles in cancer therapy. Therefore, introducing new therapeutic agents for cancer remains a priority to increase the range of effective treatments. Terpenoids, a large group of secondary metabolites, are derived from plant sources and are composed of several isoprene units. The high diversity of terpenoids has drawn attention to their potential anticancer and pharmacological activities. Some terpenoids exhibit an anticancer effect by triggering various stages of cancer progression, for example, suppressing the early stage of tumorigenesis via induction of cell cycle arrest, inhibiting cancer cell differentiation and activating apoptosis. At the late stage of cancer development, certain terpenoids are able to inhibit angiogenesis and metastasis via modulation of different intracellular signaling pathways. Significant progress in the identification of the mechanism of action and signaling pathways through which terpenoids exert their anticancer effects has been highlighted. Hence, in this review, the anticancer activities of twenty-five terpenoids are discussed in detail. In addition, this review provides insights on the current clinical trials and future directions towards the development of certain terpenoids as potential anticancer agents.
Language	English
Publishing date	2022-02-22
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2527080-1
ISSN	2072-6694
ISSN	2072-6694
DOI	10.3390/cancers14051100
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Article: Diosmetin Exerts Synergistic Effects in Combination with 5-Fluorouracil in Colorectal Cancer Cells.

Kamran, Sareh / Sinniah, Ajantha / Chik, Zamri / Alshawsh, Mohammed Abdullah

Biomedicines

2022 Volume 10, Issue 3

Abstract: 5-Fluorouracil (5-FU) is a chemotherapeutic medication commonly used to treat colorectal cancer (CRC); however, the drug-associated adverse effects and toxicity have greatly affected its clinical use. Exploring another therapeutic strategy that lowers ... ...

Abstract	5-Fluorouracil (5-FU) is a chemotherapeutic medication commonly used to treat colorectal cancer (CRC); however, the drug-associated adverse effects and toxicity have greatly affected its clinical use. Exploring another therapeutic strategy that lowers the toxicity of 5-FU while having a synergistic effect against CRC is thus a viable option. Diosmetin, a natural flavonoid, has been shown to inhibit the proliferation of many cancer cells, including CRC cells. This study aims to investigate the synergistic effect of diosmetin and 5-FU on HCT116 and HT29 colorectal cancer cells and to explore the apoptotic activity of this combination. The MTT assay was used to assess the viability of cells treated with monotherapy and combination therapy. The combination index (CI) and dose reduction index (DRI) were calculated using the CompuSyn software (version 1.0). The SynergyFinder 2.0 software was used to calculate the synergy score, while the Combenefit software was employed to perform isobologram analysis and synergism determination. The AO/PI double staining technique was used to detect the apoptotic characteristics of cells, whereas the flow cytometry technique was used to investigate the apoptosis induction and cell cycle arrest in cells. The combination of 5-FU and diosmetin showed a synergistic effect in HCT116 cells with a mean CI value of 0.66 ± 0.4, and an additive effect in HT29 cells with a CI value of 1.0 ± 0.2. The DRI of 5-FU in HCT116 cells was three times lower in the combination therapy compared to monotherapy of 5-FU. AO/PI microscopic examination and Annexin V analysis revealed that the combination-treated cells had more apoptotic cells than the monotherapy-treated cells, which was activated mainly through intrinsic apoptosis pathway. HCT116 cell death was confirmed by mitotic arrest in the G2/M phase. Our findings suggest that 5-FU/diosmetin combination exhibits synergistic effect against HCT116 cancer cells, and potentially reduces the unfavorable adverse effect of 5-FU while enhancing the anticancer efficacy by inducing apoptosis and interrupting mitosis. Further research studies are needed to validate the combination's anti-tumorigenic activities in a xenograft animal model.
Language	English
Publishing date	2022-02-24
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2720867-9
ISSN	2227-9059
ISSN	2227-9059
DOI	10.3390/biomedicines10030531
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Article ; Online: Worsening air pollution an unfamiliar cause of low vitamin D levels

Jai Aditya Jhamb / Sanjiv Rampal / Ashish Jaiman / Ajantha Sinniah / Jia Bei Tong / Aryaman Jaiman

Ķazaķstannyṇ Klinikalyķ Medicinasy, Vol 20, Iss 5, Pp 4-

A systematic literature review

2023 Volume 8

Abstract: Air pollution is widely recognized as a future biohazard, yet its direct effects on human health, particularly in relation to bone health and vitamin D levels, are inadequately understood. While the detrimental impact on respiratory and cardiovascular ... ...

Abstract	Air pollution is widely recognized as a future biohazard, yet its direct effects on human health, particularly in relation to bone health and vitamin D levels, are inadequately understood. While the detrimental impact on respiratory and cardiovascular health is well-documented, the correlation with vitamin D deficiency remains weak. To explore the relationship between air pollution and vitamin D levels, an extensive search of scientific literature was conducted. This comprehensive search encompassed databases such as PubMed, Cochrane Library, and DOAJ, while also examining the bibliographies of relevant articles. The inclusion criteria focused on studies that specifically investigated the association between air pollution and vitamin D levels, while excluding systematic reviews, case reports, editor's letters, and studies lacking pertinent explanations or causative factors. Each included study underwent rigorous evaluation of its methodological quality, with data extraction performed to assess the reliability and robustness of the evidence for each research question. The majority of studies have consistently demonstrated a negative correlation between ambient air pollution and vitamin D levels in humans. Several mechanisms have been proposed to explain this relationship, including reduced exposure to sunlight due to increased air pollution, production of reactive oxygen particles, and inflammation leading to decreased vitamin D synthesis. Moreover, certain pollutants, such as particulate matter and nitrogen dioxide, have been found to have a more pronounced impact on vitamin D levels. Variables such as age, gender, season, and geographical location may also influence the association between air pollution and vitamin D levels. Lifestyle factors, including indoor confinement and pre-existing vitamin D deficiency, may exacerbate the detrimental effects of air pollution. In conclusion, air pollution detrimentally affects vitamin D levels primarily through increased body inflammation and the generation of free ...
Keywords	Air pollution ; vitamin D levels ; dietary supplements ; and free radicals ; Internal medicine ; RC31-1245 ; Specialties of internal medicine ; RC581-951
Subject code	333
Language	English
Publishing date	2023-10-01T00:00:00Z
Publisher	National Scientific Medical Center
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Diosmetin Exerts Synergistic Effects in Combination with 5-Fluorouracil in Colorectal Cancer Cells

Sareh Kamran / Ajantha Sinniah / Zamri Chik / Mohammed Abdullah Alshawsh

Biomedicines, Vol 10, Iss 531, p

2022 Volume 531

Abstract	5-Fluorouracil (5-FU) is a chemotherapeutic medication commonly used to treat colorectal cancer (CRC); however, the drug-associated adverse effects and toxicity have greatly affected its clinical use. Exploring another therapeutic strategy that lowers the toxicity of 5-FU while having a synergistic effect against CRC is thus a viable option. Diosmetin, a natural flavonoid, has been shown to inhibit the proliferation of many cancer cells, including CRC cells. This study aims to investigate the synergistic effect of diosmetin and 5-FU on HCT116 and HT29 colorectal cancer cells and to explore the apoptotic activity of this combination. The MTT assay was used to assess the viability of cells treated with monotherapy and combination therapy. The combination index (CI) and dose reduction index (DRI) were calculated using the CompuSyn software (version 1.0). The SynergyFinder 2.0 software was used to calculate the synergy score, while the Combenefit software was employed to perform isobologram analysis and synergism determination. The AO/PI double staining technique was used to detect the apoptotic characteristics of cells, whereas the flow cytometry technique was used to investigate the apoptosis induction and cell cycle arrest in cells. The combination of 5-FU and diosmetin showed a synergistic effect in HCT116 cells with a mean CI value of 0.66 ± 0.4, and an additive effect in HT29 cells with a CI value of 1.0 ± 0.2. The DRI of 5-FU in HCT116 cells was three times lower in the combination therapy compared to monotherapy of 5-FU. AO/PI microscopic examination and Annexin V analysis revealed that the combination-treated cells had more apoptotic cells than the monotherapy-treated cells, which was activated mainly through intrinsic apoptosis pathway. HCT116 cell death was confirmed by mitotic arrest in the G2/M phase. Our findings suggest that 5-FU/diosmetin combination exhibits synergistic effect against HCT116 cancer cells, and potentially reduces the unfavorable adverse effect of 5-FU while enhancing the anticancer ...
Keywords	synergistic effect ; dose reduction index ; combination index ; diosmetin ; 5-fluorouracil ; colorectal cancer ; Biology (General) ; QH301-705.5
Subject code	610
Language	English
Publishing date	2022-02-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article: Distribution of Causative Microorganisms in Diabetic Foot Infections: A Ten-Year Retrospective Study in a Tertiary Care Hospital in Central Malaysia.

Hadi, Parichehr / Rampal, Sanjiv / Neela, Vasantha Kumari / Cheema, Manraj Singh / Sarawan Singh, Sandeep Singh / Kee Tan, Eng / Sinniah, Ajantha

Antibiotics (Basel, Switzerland)

2023 Volume 12, Issue 4

Abstract: Diabetes mellitus is a global pandemic, especially in Southeast Asia. Diabetic foot infection (DFI) is a common complication of this condition and causes significant morbidity and mortality in those affected. There is a lack of locally published data on ... ...

Abstract	Diabetes mellitus is a global pandemic, especially in Southeast Asia. Diabetic foot infection (DFI) is a common complication of this condition and causes significant morbidity and mortality in those affected. There is a lack of locally published data on the types of microorganisms and empirical antibiotics being prescribed. This paper highlights the importance of local microorganism culture and antibiotic prescription trends among diabetic foot patients in a tertiary care hospital in central Malaysia. This is a retrospective, cross-sectional study of data taken from January 2010 to December 2019 among 434 patients admitted with diabetic foot infections (DFIs) using the Wagner classification. Patients between the ages of 58 and 68 years old had the highest rate of infection.
Language	English
Publishing date	2023-03-31
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2681345-2
ISSN	2079-6382
ISSN	2079-6382
DOI	10.3390/antibiotics12040687
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Article ; Online: Punicalagin Regulates Apoptosis-Autophagy Switch via Modulation of Annexin A1 in Colorectal Cancer.

Ganesan, Thanusha / Sinniah, Ajantha / Chik, Zamri / Alshawsh, Mohammed Abdullah

Nutrients

2020 Volume 12, Issue 8

Abstract: Punicalagin (PU), a polyphenol extracted from pomegranate ( ...

Abstract	Punicalagin (PU), a polyphenol extracted from pomegranate (
MeSH term(s)	Adenocarcinoma/drug therapy ; Annexin A1/drug effects ; Antineoplastic Agents/pharmacology ; Autophagic Cell Death/drug effects ; Colorectal Neoplasms/drug therapy ; HCT116 Cells ; Humans ; Hydrolyzable Tannins/pharmacology ; Plant Extracts/pharmacology ; Pomegranate/chemistry
Chemical Substances	Annexin A1 ; Antineoplastic Agents ; Hydrolyzable Tannins ; Plant Extracts ; punicalagin (65995-63-3)
Language	English
Publishing date	2020-08-13
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2518386-2
ISSN	2072-6643 ; 2072-6643
ISSN (online)	2072-6643
ISSN	2072-6643
DOI	10.3390/nu12082430
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Article ; Online: Evaluation of Anti-Tumorigenic Effects of Diosmetin against Human Colon Cancer Xenografts in Athymic Nude Mice.

Koosha, Sanaz / Mohamed, Zahurin / Sinniah, Ajantha / Alshawsh, Mohammed A

Molecules (Basel, Switzerland)

2019 Volume 24, Issue 14

Abstract: Colon cancer is the third most common type of cancer in the world. Diosmetin (Dis), a ... ...

Abstract	Colon cancer is the third most common type of cancer in the world. Diosmetin (Dis), a natural
MeSH term(s)	Analgesics/pharmacology ; Animals ; Apoptosis/drug effects ; Cell Line, Tumor ; Colonic Neoplasms/drug therapy ; Colonic Neoplasms/pathology ; Disease Models, Animal ; Female ; Flavonoids/pharmacology ; HCT116 Cells ; Humans ; Mice ; Mice, Nude ; Toxicity Tests, Acute ; Tumor Burden/drug effects ; Xenograft Model Antitumor Assays
Chemical Substances	Analgesics ; Flavonoids ; diosmetin (TWZ37241OT)
Language	English
Publishing date	2019-07-10
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	1413402-0
ISSN	1420-3049 ; 1431-5165 ; 1420-3049
ISSN (online)	1420-3049
ISSN	1431-5165 ; 1420-3049
DOI	10.3390/molecules24142522
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Article: Endogenous Annexin-A1 Negatively Regulates Mast Cell-Mediated Allergic Reactions.

Sinniah, Ajantha / Yazid, Samia / Bena, Stefania / Oliani, Sonia M / Perretti, Mauro / Flower, Rod J

Frontiers in pharmacology

2019 Volume 10, Page(s) 1313

Abstract: Mast cell stabilizers like cromoglycate and nedocromil are mainstream treatments for ocular allergy. Biochemical ... ...

Abstract	Mast cell stabilizers like cromoglycate and nedocromil are mainstream treatments for ocular allergy. Biochemical studies
Language	English
Publishing date	2019-11-13
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2587355-6
ISSN	1663-9812
ISSN	1663-9812
DOI	10.3389/fphar.2019.01313
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Article ; Online: Investigation into the Molecular Mechanisms underlying the Anti-proliferative and Anti-tumorigenesis activities of Diosmetin against HCT-116 Human Colorectal Cancer.

Koosha, Sanaz / Mohamed, Zahurin / Sinniah, Ajantha / Alshawsh, Mohammed A

Scientific reports

2019 Volume 9, Issue 1, Page(s) 5148

Abstract: Diosmetin (Dis) is a bioflavonoid with cytotoxicity properties against variety of cancer cells including hepatocarcinoma, breast and colorectal (CRC) cancer. The exact mechanism by which Dis acts against CRC however, still remains unclear, hence in this ... ...

Abstract	Diosmetin (Dis) is a bioflavonoid with cytotoxicity properties against variety of cancer cells including hepatocarcinoma, breast and colorectal (CRC) cancer. The exact mechanism by which Dis acts against CRC however, still remains unclear, hence in this study, we investigated the possible molecular mechanisms of Dis in CRC cell line, HCT-116. Here, we monitored the viability of HCT-116 cells in the presence of Dis and investigated the underlying mechanism of Dis against HCT-116 cells at the gene and protein levels using NanoString and proteome profiler array technologies. Findings demonstrated that Dis exhibits greater cytotoxic effects towards HCT-116 CRC cells (IC50 = 3.58 ± 0.58 µg/ml) as compared to the normal colon CCD-841 cells (IC50 = 51.95 ± 0.11 µg/ml). Arrests of the cells in G2/M phase confirms the occurrence of mitotic disruption via Dis. Activation of apoptosis factors such as Fas and Bax at the gene and protein levels along with the release of Cytochrome C from mitochondria and cleavage of Caspase cascades indicate the presence of turbulence as a result of apoptosis induction in Dis-treated cells. Moreover, NF-ƙB translocation was inhibited in Dis-treated cells. Our results indicate that Dis can target HCT-116 cells through the mitotic disruption and apoptosis induction.
MeSH term(s)	Antineoplastic Agents/pharmacology ; Colorectal Neoplasms/drug therapy ; Colorectal Neoplasms/metabolism ; Colorectal Neoplasms/pathology ; Flavonoids/pharmacology ; G2 Phase Cell Cycle Checkpoints/drug effects ; HCT116 Cells ; Humans ; M Phase Cell Cycle Checkpoints/drug effects
Chemical Substances	Antineoplastic Agents ; Flavonoids ; diosmetin (TWZ37241OT)
Language	English
Publishing date	2019-03-26
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2615211-3
ISSN	2045-2322 ; 2045-2322
ISSN (online)	2045-2322
ISSN	2045-2322
DOI	10.1038/s41598-019-41685-1
Database	MEDical Literature Analysis and Retrieval System OnLINE

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